2-102341256-C-T

Variant names:

• chr2-102341256-C-T
• rs1420101
• NM_016232.5:c.610+428C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016232.5(IL1RL1):​c.610+428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,240,744 control chromosomes in the GnomAD database, including 85,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9542 hom., cov: 29)
  • Exomes 𝑓: 0.37 (76049 hom.)
• Consequence: IL1RL1 NM_016232.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 131 publications found

Genes affected

IL1RL1 (HGNC:5998): (interleukin 1 receptor like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.610+428C>T		intron	N/A	NP_057316.3
	IL1RL1	NM_003856.4		c.610+428C>T		intron	N/A	NP_003847.2
	IL1RL1	NM_001282408.2		c.259+428C>T		intron	N/A	NP_001269337.1	Q01638-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.610+428C>T		intron	N/A	ENSP00000233954.1	Q01638-1
	IL1RL1	ENST00000311734.6	TSL:1	c.610+428C>T		intron	N/A	ENSP00000310371.2	Q01638-2
	IL1RL1	ENST00000427077.1	TSL:1	n.679C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000391120.1	Q01638-3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53264 AN: 150574 Hom.: 9536 Cov.: 29

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.326 AC: 34721 AN: 106446 AF XY: 0.333

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.389

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.372 AC: 405350 AN: 1090062 Hom.: 76049 Cov.: 23 AF XY: 0.372 AC XY: 198512 AN XY: 533282

African (AFR) AF: 0.316 AC: 6725 AN: 21308

American (AMR) AF: 0.224 AC: 3233 AN: 14440

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 4120 AN: 13642

East Asian (EAS) AF: 0.415 AC: 4282 AN: 10310

South Asian (SAS) AF: 0.359 AC: 23035 AN: 64224

European-Finnish (FIN) AF: 0.312 AC: 8089 AN: 25966

Middle Eastern (MID) AF: 0.491 AC: 2010 AN: 4090

European-Non Finnish (NFE) AF: 0.378 AC: 339277 AN: 897298

Other (OTH) AF: 0.376 AC: 14579 AN: 38784

GnomAD4 genome AF: 0.354 AC: 53305 AN: 150682 Hom.: 9542 Cov.: 29 AF XY: 0.352 AC XY: 25846 AN XY: 73398

African (AFR) AF: 0.335 AC: 13729 AN: 40936

American (AMR) AF: 0.292 AC: 4412 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1075 AN: 3462

East Asian (EAS) AF: 0.437 AC: 2230 AN: 5100

South Asian (SAS) AF: 0.362 AC: 1731 AN: 4782

European-Finnish (FIN) AF: 0.320 AC: 3267 AN: 10196

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.379 AC: 25673 AN: 67818

Other (OTH) AF: 0.374 AC: 783 AN: 2096

Alfa AF: 0.368 Hom.: 51466

Bravo AF: 0.347

Asia WGS AF: 0.416 AC: 1448 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1420101; hg19: chr2-102957716; COSMIC: COSV52112335; COSMIC: COSV52112335;